Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of

Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of

Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of

Emodin inhibits migration and invasion of DLD-1(PRL-3)cells via inhibition of PRL-3phosphatase activity

Young-Min Han a ,c ,Su-Kyung Lee a ,Dae Gwin Jeong b ,Seong Eon Ryu b ,Dong Cho Han a ,c ,Dae Keun Kim d ,⇑,Byoung-Mog Kwon a ,c ,⇑

a

Laboratory of Chemical Genomics and Biology,Korea Research Institute of Bioscience and Biotechnology,1125Gwahakro,Yoosunggu,Daejeon 305-600,Republic of Korea b

Proteomics Research Center,Korea Research Institute of Bioscience and Biotechnology,1125Gwahakro,Yoosunggu,Daejeon 305-600,Republic of Korea c

University of Science and Technology,Daejeon 305-333,Republic of Korea d

College of Pharmacy,Woosuk University,Samrye 565-701,Republic of Korea

a r t i c l e i n f o Article history:

Received 10September 2011Revised 29October 2011Accepted 2November 2011

Available online 9November 2011Keywords:Emodin Metastasis PRL-3Migration Invasion

a b s t r a c t

Anthraquinones have been reported as phosphatase inhibitors.Therefore,anthraquinone derivatives were screened to identify a potent phosphatase inhibitor against the phosphatase of regenerating liver-3(PRL-3).Emodin strongly inhibited phosphatase activity of PRL-3with IC 50values of 3.5l M and blocked PRL-3-induced tumor cell migration and invasion in a dose-dependent manner.Emodin res-cued the phosphorylation of ezrin,which is a known PRL-3substrate.The results of this study reveal that emodin is a PRL-3inhibitor and a good lead molecule for obtaining a selective PRL-3inhibitor.

Ó2011Elsevier Ltd.All rights reserved.

Emodin inhibits migration and invasion of DLD-1 (PRL-3) cells via inhibition of

Tumor progression is a complex process that includes malig-nant transformation,proliferation,invasion,and metastasis of can-cer cells.Cancer cell invasion and metastasis are critical processes and are the major causes of death for cancer patients.1,2Approxi-mately 90%of all cancer deaths arise from the metastatic spread of tumors.3To overcome this problem,a greater understanding of the biology of metastasis and the development of novel therapeu-tics that specifically target metastasis and metastatic progression are required.4–6Colorectal cancer (CRC)is the third most com-monly diagnosed cancer in males and the second in females,and caused over 1.2million new cancer cases and approximately 608,700deaths in 2008.7CRC is also the third most common type of cancer and cause of cancer-related deaths in the United States in men and women with an estimated 102,900new cases in 2010.8Many CRC patients suffer from the unexpected development of metastasis,after the curative resection of their primary tumors,and approximately 50%develop liver metastasis at some point dur-ing their disease.9

The phosphatase of regenerating liver family (PRL-1,-2,and -3)constitute three closely related intracellular enzymes that possess the protein-tyrosine phosphatase (PTP)active site.10Saha et al.

0960-894X/$-see front matter Ó2011

Elsevier Ltd.All rights reserved.doi:10.1016/j.bmcl.2011.11.008

⇑Corresponding authors.Tel.:+82428604557;fax:+82428612675(B.-M.K.).

E-mail addresses:dkkim@mail.woosuk.ac.kr (D.K.Kim),kwonbm@kribb.re.kr (B.-M.Kwon).

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